Definitions and measurement of negative symptoms in schizophrenia

Negative symptoms of schizophrenia represent deficits in different domains, e.g. loss or diminution in emotions, thinking and movement. Persistent primary negative symptoms are considered to be part of the schizophrenia disease process and represent an unmet need for treatment, while secondary negative symptoms are associated with positive symptoms of schizophrenia, other mental disorders (e.g. depression, substance abuse), extrapyramidal symptoms, social deprivation, etc. Validated rating scales are helpful in the evaluation and measurement of negative symptoms. Current consensus supports the focus on the following five domains (five ‘As’): blunted affect, alogia, anhedonia, asociality, and avolition.

Psychosocial/non-pharmacologic treatment of negative symptoms

Current best practice regarding the treatment of negative symptoms of schizophrenia supports the use of psychological interventions in addition to medication. This chapter reviews the literature evaluating different non-pharmacological approaches to treating these symptoms. Meta-analytic studies suggest that social skills training, music therapy, non-invasive brain stimulation, mindfulness, and exercise-based interventions are all effective at improving negative symptoms, relative to treatment as usual (TAU). Effect sizes for these interventions range from small to moderate. The long-term benefits of these interventions are currently unclear, and there has been some debate as to whether the impact of these interventions constitute consistent, clinically meaningful change. Evidence for other therapies such as arts therapies other than music therapy, cognitive behavioural therapies for psychosis, neurocognitive therapies, and family-based interventions is more inconsistent. As a result, primary negative symptoms of schizophrenia can still be considered an important unmet therapeutic need where more research is needed.

The patients’ view

The use and the choice of standardized assessment tools are necessary for improving identification of negative symptoms and for testing new efficient therapies. Most of the scales on negative symptoms are based on observer rating. Compared to these scales, self-assessments have been overlooked. Nevertheless, they are quite relevant since they are generally simple; they allow the patients to report their own symptoms and so are complementary to the evaluations based on observer ratings; they require the patient’s participation and so improve their involvement in the treatment; they are time-efficient and can be very useful for identification of negative symptoms at the onset of illness. Among the self-assessments, we can distinguish those designed and validated in patients with schizophrenia and others that can be used in schizophrenia while they have been validated in other populations. Among the first group, two recent scales have supplanted old scales, the Motivation and Pleasure Scale–Self-Report (MAP–SR) and the Self-evaluation of Negative Symptoms (SNS). The last one presents all the psychometric properties required. Among the second group, the most used scales are focused on anhedonia and apathy which assess these dimensions in schizophrenia but also in various psychiatric and neurological disorders; the most well-known are the Social Anhedonia Scale (SAS), the Physical Anhedonia Scale (PAS), and more recently are, on the one hand, the Self-reported Apathy Evaluation Scale (AES-S) and on the other, the Temporal Experience of Pleasure Scale (TEPS) and the Anticipatory and Consummatory Interpersonal Pleasure Scale (ACIPS) which distinguish anticipation and consummatory pleasures.

Long-term course of negative symptoms in schizophrenia

The chapter focuses on the relationship of negative and positive symptoms in schizophrenia. Negative symptoms should be evaluated in a relation to positive symptoms both cross-sectionally and long term (prospectively/retrospectively). Two types of long-term interaction between negative and positive symptoms could be distinguished: (1) relatively synchronized, and (2) relatively desynchronized. Synchronization of negative and positive symptoms is characterized by their unidirectional long-term course. Desynchronization is characterized by their bidirectional long-term relations: (1) negative schizophrenia with minimal positive symptoms at the beginning of the disease and further progression of negative symptoms; or (2) schizophrenia with negative symptoms ‘that stopped at the very beginning’, and the later course is characterized by positive symptoms. Considering every single time point of the long-term relationship between negative and positive symptoms (cross-sectionally), the chapter describes the concept of ‘mutual/common syndromes’ (consisting of both positive and negative symptoms) at different stages of schizophrenia, including residual deficit states.

Basic symptoms in deficit states and their relation to negative symptoms

Basic symptoms are subtle, subjectively experienced disturbances in mental processes including thinking, speech, attention, perception, drive, stress tolerance, and affect, originally described by Gerd Huber. Basic symptoms are present in prodromal, psychotic, and residual/deficit states of schizophrenia and have been conceptualized as the most immediate psychopathological expression of the neurobiological abnormalities underlying the development and persistence of psychosis. Basic symptoms are currently mostly recognized for their potential to detect psychosis prior to the first psychotic episode and, thus, for their ability to herald persistent positive symptoms. Although initially described to facilitate understanding of deficit states in schizophrenia, their contribution to negative symptoms has less been studied, although the evaluation of basic symptoms helps in improving understanding of the psychopathology—including differentiation of primary and secondary negative symptoms—and course of schizophrenia and in planning better treatment.

Pharmacologic treatment of negative symptoms

During the last decade negative symptoms in schizophrenia became a legitimate indication for potential drug targets. Significant progress has been made to improve measurement of negative symptoms, to distinguish between primary and secondary negative symptoms, and the importance of predominant negative symptoms was underlined. However, few clinical trials focused on primary and/or predominant negative symptoms. A large meta-analysis found that second-generation antipsychotics (SGA) had the greatest efficacy for negative symptoms, followed by first-generation antipsychotics (FGA), combination treatments, antidepressants, and glutamatergic medications. The included studies, however, were not specifically designed to measure negative symptoms. With respect to patients with predominant negative symptoms, in the largest trial conducted so far, the SGA cariprazine was superior to its comparator, risperidone. For medication classes other than antipsychotics and antidepressants, no reliable support was found that would substantiate evidence-based recommendations for using these agents in the treatment of negative symptoms in clinical practice.